Is CDH12 p.Ser529Pro (c.1585T>C) pathogenic?

CDH12 p.Ser529Pro (c.1585T>C) is classified Likely benign in CDH12 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-06). AlphaMissense: likely benign (0.1162); Rare (popmax 0.307%, afr).

How common is CDH12 p.Ser529Pro (c.1585T>C) in the general population?

CDH12 p.Ser529Pro (c.1585T>C) is rare (popmax 0.307%, afr) (gnomAD).

What do computational predictors say about CDH12 p.Ser529Pro (c.1585T>C)?

AlphaMissense predicts likely benign (score 0.1162) — an in-silico prediction, not a clinical call.

CDH12 p.Ser529Pro

c.1585T>C · rs143459013 · VCV739263

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1162 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.307%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1162	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -9.23	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.67	GERP -3.8, phastCons 0.013
Regional constraint	o/e 1.00	unconstrained · MANE · 223 kb · p 0.95 · regional, not allelic
Overall
CADD	11.28	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.307% African / African-American · 230/74,982 alleles

Filtering AF 0.274% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.262%

Overall 0.0151% 244/1,612,124 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.307%	326
Middle Eastern	0.033%	3,028
Admixed American	0.01%	9,989
Remaining individualsnot grpmax-eligible	0.00801%	12,486
European (non-Finnish)	8.49e-05%	1,178,473

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CDH12
Protein: p.Ser529Pro
Coding: c.1585T>C
MANE Select: NM_004061
dbSNP: rs143459013
Type: single nucleotide variant
Location: chr5:21760606 (GRCh38)
Gene constraint: LOEUF 0.668 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.19
Residue 529: the cadherin 5 domain

Full CDH12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH12 c.1003-3C>T Benign ★★ same type
CDH12 p.Asp780= Likely benign ★★ same type
CDH12 p.Gln60= Benign ★★ same type
CDH12 p.Glu349Asp Benign ★★ ⚠ same type
CDH12 p.Glu34Gln Benign ★★ same type
CDH12 p.Ile475Thr Benign ★★ ⚠ same type
CDH12 p.Ile598= Likely benign ★★ same type
CDH12 p.Pro213= Benign ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cdh12-p-ser529pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown